Anxiety disorders are widespread and costly. Social anxiety disorder (SAD) is one of the most common anxiety disorders, and can lead to significant functional impairment. Despite the prevalence of behavior therapy interventions for anxiety disorders, including SAD, the neural mediators of behavioral treatment for anxiety are understudied. Here, we propose research that will elucidate the neurocognitive effects of behavior therapy for SAD. Secondarily, it will allow for the comparison of two distinct types of behavior therapy on a neural level. Participants will be randomized to either cognitive-behavioral therapy (CBT), a wait-list control (WL), or a newer form of behavioral therapy, acceptance and commitment therapy (ACT). Primary comparisons will be between CBT and WL. Secondary comparisons will be between CBT and ACT. Using functional magnetic resonance imaging (fMRI) to scan clients with SAD before and after the 12- week CBT/ACT or a 12-week wait-list control period while they complete a threat processing task that has been used extensively with non-clinical samples (the Linguistic Processing of Affect Task, or L-PAT), we expect to see several changes in neural activations after treatment, relative to the wait list control period. Namely, we expect reductions in the amygdala response to negatively-valenced faces after treatment. We also expect a post-treatment increase in prefrontal activation, specifically in the right ventrolateral prefrontal cortex (RVLPFC), which is implicated in the processing of negative affect. Previous work with non-clinical samples has suggested that the RVLPFC may work to inhibit or dampen the amygdala response to threat; therefore, we predict that therapy will work to strengthen this process. We expect to see a post-treatment difference in the functional connectivity of those two regions (the amygdala and RVLPFC), such that activations in the RVLPFC and amygdala will be more strongly negatively correlated after treatment. We predict that the degree of symptom improvement after treatment will also correlate with the expected changes in neural activation, outlined above. We also present some exploratory hypotheses about differences between CBT and ACT that may emerge at a neural level. The proposed work will be one of the first investigations of the neural mediators of behavior therapy treatment for anxiety, and would also be the first study to compare two behavior therapy treatments on a neural level. This work will shed light on the characteristics of anxiety disorders and improve understanding of the treatments commonly used for anxiety. PUBLIC HEALTH RELEVANCE: The proposed work would be one of the first investigations of the neural mediators of behavior therapy treatment for anxiety, and would also be the first study to compare two behavior therapy treatments on a neural level. This work will shed light on the characteristics of anxiety disorders and improve understanding of the treatments commonly used for anxiety. [unreadable] [unreadable] [unreadable]